WASHINGTON — Teriparatide appeared to increase lumbar spine bone mineral density and showed some promise in reducing nonvertebral fractures in patients on glucocorticoid therapy with low bone mineral density or a prior fragility fracture, according to data presented at an international symposium sponsored by the National Osteoporosis Foundation.
“In patients with glucocorticoid-induced osteoporosis treated with teriparatide or alendronate for 18 months, teriparatide resulted in significantly greater increases in lumbar spine bone mineral density (BMD) compared with alendronate. Significantly fewer patients had new vertebral fractures with teriparatide, compared with the alendronate group,” said Margaret R. Warner, Ph.D., a researcher with Eli Lilly & Co., which funded this trial.
At 18 months, lumbar spine BMD increased 7.2% for patients treated with teriparatide and 3.4% for those treated with alendronate. Differences could be seen between the two treatment groups as early as 6 months.
Teriparatide (Forteo), made by Eli Lilly, contains recombinant human parathyroid hormone (1–34) and is currently indicated for the treatment of postmenopausal women with osteoporosis who are at high risk for fracture. The drug also is indicated to increase bone mass in men with primary or hypogonadal osteoporosis who are at high risk for fracture. Teriparatide is the only osteoporosis drug shown to stimulate new bone growth.
Glucocorticoid therapy is the most common cause of secondary osteoporosis. Currently, only the bisphosphonates risedronate (Actonel, made by Procter & Gamble Pharmaceuticals) and alendronate (Fosamax, made by Merck & Co.) are indicated for the prevention and treatment of glucocorticoid-induced osteoporosis in men and women receiving glucocorticoids in a daily dosage equivalent to 7.5 mg or greater of prednisone and who have low BMD.
The trial included men and women at least 21 years of age who had taken a minimum dose of 5 mg/day of prednisone (or its equivalent) for 3 months or longer prior to screening. All patients had total hip, femoral neck, or lumbar spine T scores of at most −2.0 or at most −1.0 with a prior fragility fracture. A total of 428 patients (80% women) were randomized to receive 20 mcg/day teriparatide injection and an oral placebo tablet or 10 mg/day oral alendronate and an injectable placebo. All patients in the trial received calcium and vitamin D supplements. Patients were followed for 18 months.
The primary end point was the effect of teriparatide on lumbar spine BMD in patients with glucocorticoid-induced osteoporosis compared with alendronate. The researchers also looked at the effect of teriparatide versus alendronate on total hip and femoral neck BMD, on markers of bone turnover, and on the incidence of vertebral and nonvertebral fractures.
BMD was assessed using dual-energy x-ray absorptiometry. Vertebral fractures were assessed using semiquantitative visual scoring of radiographs taken at baseline and at 18 months. Nonvertebral fractures were assessed with radiograph or radiologist report. Both vertebral and nonvertebral fractures were assessed at a central reader site.
In addition, markers of bone turnover were analyzed in roughly half of the patients in each group. Adverse event data were collected throughout.
At baseline, both groups were fairly evenly matched in terms of gender, race, age, average prednisone dose, and average duration of prednisone use. Both groups were evenly matched in average BMD at the total hip, femoral neck, and lumbar spine, and vertebral and nonvertebral fractures. Three-quarters of patients in both groups had rheumatologic disease. Rheumatoid arthritis was the most common, accounting for 69% of those in the alendronate group and 61% of those in the teriparatide group.
Total hip BMD rose 3.6% for the teriparatide group, versus 2.2% for the alendronate group. Femoral neck BMD rose 3.7% for the teriparatide group, versus 2.1% for the alendronate group.
In terms of biomarkers of bone turnover, the researchers measured serum procollagen type 1 N-propeptide (P1NP)–a marker of bone formation—and serum C-terminal telopeptide of type 1 collagen (CTX)–a marker of bone resorption. “In the teriparatide group, there were increases in serum P1NP and CTX, whereas with the antiresorptive agent there were decreases in serum P1NP and CTX,” said Dr. Warner.
Adverse event profiles were similar between groups. In the teriparatide group there were 182 adverse events, with 45 considered serious. There were 170 adverse events in the alendronate group, and 39 were considered serious.